Starting at level 59 (as high as I could get on my first playthrough). The enemies scale in difficulty with your level, so this guide is as hard as it gets.

Earthborn

Ruthless

Adept

Why Adept?

I decided to play through as an Adept because of how dramatically different the gameplay is compared to EVERY OTHER THIRD PERSON SHOOTER. I played through Mass Effect 1 & 2 as an Infiltrator (the sniper class) and had no idea how fun the game could be if you don't play Mass Effect as a generic third person shooter.

Vanguard is also an incredibly fun class to play as, but not on Insane difficulty (or Gold for multiplayer). The Jump ability and lots of fast paced shotgun action is super fun, but you will die A LOT on the harder difficulties.

PUT NO POINTS INTO WARP OR SINGULARITY! You are going to rely on her Stasis pretty heavily, and you don't want her using powers and killing the cooldown (yes I know there's a setting to change this, but I want the second squadmate to use their powers at will). To get 0 points in Singularity, reset her powers in the Med Bay on the Normandy.

Use whoever you like for the second squadmate. I will be using Javik (when I can) simply for the extra Biotic detonations.

Sidequests & Cutscenes

I'll be making videos for all of the main missions and 'action' sidequests, but I will be skipping ALL cutscenes and 'talking' sidequests.

@John Tarr Just watched the first N7 mission and heard about reusing the maps. The multiplayer trailer explained why. Shepard got the objective and moved on in the single-player, and now an elite team needs to hold it and fend off enemies. Also, after you complete some of these missions Hackett says as much.

Given John's playstyle, I would recommend Sentinel as an alternative to Adept. You get Warp and Throw as before, plus the added bonus of Overload, which is useful against Shields on the Atlus. Also, you can activate a shield which can save your life on Insane (although at the cost of a slightly longer cooldown)

I don't agree with some of this advice. I've beaten the game twice as an adept on insanity (once with Kaidan alive and once with Ashley), and I did it without too much difficulty. The biggest problem I see is people saying to ignore singularity. Actually, singularity is what I used to get the vast majority of my kills throughout the game. When facing most enemies, I would have Liara cast singularity and then Shepard would immediately follow up with warp or reave.

Singularity/warp will kill just about every regular enemy in the game. Singularity/reave doesn't kill quite as instantaneously as singularity/warp, but the enemy will die quickly from the damage over time, reave can hit multiple enemies at once, and it can reduce damage to Shepard by up to 40 percent, which really helps on insanity. Also, warp can detonate reave, which really helps against heavily armored enemies like Brutes. Even spamming warp by itself is the best way to take down heavy armor. Once reave became available, I switched from singularity/warp to singularity/reave in most situations. Singularity/warp should still be used on synthetic enemies like Geth, though.

For shielded enemies like Centurions or Cerberus Engineers, I have Kaidan/EDI/Garrus use overload (a squad mate with overload is essential when facing heavily shielded enemies like Atlas mechs) to strip the shield, and then use the singularity and warp/reave combo. Alternatively (if the overload specialist is still cooling down), I have Liara use stasis (honestly, she doesn't need more than one level of stasis--this was the only skill of hers that I didn't max out) and then strip the shield with a headshot from the powerful (and relatively lightweight) Mantis sniper rifle. Then, I follow up with singularity and warp/reave. If Liara is knocked out or cooling down (though her cool downs are so fast that this really shouldn't be much of an issue), I have Shepard do both parts of the combo herself. With the right upgrades and equipment (the Mantis sniper and an SMG with the ultra-lightweight materials mod), my singularity was cooling down in under two seconds (it started at around 135 percent recharge and eventually went to about 150 percent by the end of the game--it was 200 percent on the new game plus), so the fact that it takes a bit longer than pull/throw to cool down becomes a moot point.

Also, a singularity field can last more than 20 seconds and take up a lot of space to pull enemies in. If a group of husks is charging, have Liara and Shepard both lay down singularity fields in strategic locations. Wait for several husks to get trapped in the field and then detonate. Singularity is also great for pulling enemies out of cover. Liara will almost never miss, and Shepard should be very accurate with a little bit of practice. Singularity is awesome. Make sure to take the upgrade that increases the duration of the field (which also allows the field to pick up additional enemies), the one that does damage over time (up to around 40 damage per second--which can be used to strip the shield off an enemy in cover if the shield is already significantly damaged), and the last one that expands the size of the field.

For other powers, I'd max out warp, taking the upgrades to detonations, lasting damage and armor-piercing. I'd take reave as a bonus power as soon as it's available (only if Kaidan is alive, and he should be because he's the best squad mate in the game due to having both overload and reave). Take the area upgrade and the two upgrades that increase damage resistance to 40 percent (the last one also increases damage and duration). For fitness, focus on the health and barrier upgrades. An adept should not be using melee combat except as a last resort. Even at close range, I preferred to use singularity to incapacitate a charging enemy like a husk. For biotic mastery, focus on the upgrades that increase damage and force, as well as the squad upgrade, since that will help both Liara and Shepard (and Kaidan if he's available). The other skills are unnecessary.